Project Summary/Abstract Stroke is a leading cause of serious long term disability. Annual incidence is approximately 800,000 in the US, and 17,000,000 worldwide. Only 10% of stroke survivors return to full normal function and activity. Over 7.2 million people in the US have survived a stroke, but continue to live with its debilitating effects. Eighty-seven percent (87%) of strokes are ischemic (damage resulting from lack of blood supply to a particular region of the brain). It is estimated that approximately fifty percent of ischemic strokes results from Emergent Large Vessel Occlusions (ELVOs), with an acute blockage of a main artery in the brain. This subgroup of stroke is particularly attractive as an initial target for therapeutic clinical trials, as the patient population and disease presentation is more homogenous, the current therapeutic paradigm is well-established, and the potential for benefit is greatest as ELVO causes the most severe and disabling type of stroke. Stream Biomedical is commercializing a therapeutic protein, recombinant human perlecan domain V (rDV), which has been shown in small animals to be significantly neuroprotective and neuroreparative (angiogenic and neurogenic), resulting in dramatic functional improvement when administered acutely after ischemic stroke. The initial target therapeutic indication is for the treatment of acute ischemic stroke resulting from ELVO, and the clinical objective is to improve functional outcomes post-stroke. The development objectives of this translational proposal are to conduct studies to determine a preference for rDV or its fragment rLG3 as the therapeutic candidate, to develop and define a preferred scalable recombinant microbial production process and conduct IND-enabling studies of the lead protein/process candidate including protein characterization, dose-range finding, pharmacodynamics, safety pharmacology and toxicology.